The prostatic environment suppresses growth of androgen-independent prostate cancer xenografts: An effect influenced by testosterone

BACKGROUND Interactions between prostate cancer cells and their surrounding stroma play an important role in the growth and maintenance of prostate tumors. To elucidate this further, we investigated how growth of androgen‐dependent (AD) LNCaP and androgen‐independent (AI) LNCaP‐19 prostate tumors was affected by different microenvironments and androgen levels. METHODS Tumor cells were implanted subcutaneously and orthotopically in intact and castrated immunodeficient mice. Orthotopic tumor growth was followed by magnetic resonance imaging (MRI). Gene expression in the tumors was evaluated by means of microarray analysis and microvessel density (MVD) was analyzed using immunohistochemistry. RESULTS The results showed that LNCaP‐19 tumors grew more rapidly at the subcutaneous site than in the prostate, where tumors were obviously inhibited. Castration of the mice did not affect ectopic tumors but did result in increased tumor growth in the prostatic environment. This effect was reversed by testosterone treatment. In contrast to LNCaP‐19, the LNCaP cells grew rapidly in the prostate and castration reduced tumor development. Gene expression analysis of LNCaP‐19 tumors revealed an upregulation of genes, inhibiting tumor growth (including ADAMTS1, RGS2 and protocadherin 20) and a downregulation of genes, promoting cell adhesion and metastasis (including N‐cadherin and NRCAM) in the slow‐growing orthotopic tumors from intact mice. CONCLUSIONS The results show that the prostatic environment has a varying impact on AD and AI tumor xenografts. Data indicate that the androgen‐stimulated prostatic environment limits growth of orthotopic AI tumors through induction of genes that inhibit tumor growth and suppression of genes that promote cell adhesion and metastasis. Prostate 69:1164–1175, 2009. © 2009 Wiley‐Liss, Inc.